Direct synthesis of aryl-annulated [c]carbazoles by gold(i)-catalysed cascade reaction of azide-diynes and arenes

Article abstract of DOI:10.1039/C8SC03525C

The gold-catalysed annulation of conjugated alkynes bearing an azido group with arenes gave annulated [c]carbazoles. Using benzene, pyrrole, and indole derivatives as the nucleophiles, benzo[c]-, pyrrolo[2,3-c]-, and indolo[2,3-c]carbazoles were produced,

Full text of DOI:10.1039/C8SC03525C

View Article Online
View Journal
Chemical
Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Kawada, S.
Ohmura, M. Kobayashi, W. Nojo, M. Kondo, Y. Matsuda, J. Matsuoka, S. Inuki, S. Oishi, C. WANG, T. Saito,
M. Uchiyama, T. Suzuki and H. Ohno, Chem. Sci., 2018, DOI: 10.1039/C8SC03525C.
This is an Accepted Manuscript, which has been through the
Volume
7 Number 1 January 2016 Pages 1–812
Royal Society of Chemistry peer review process and has been
accepted for publication.
Chemical
Science
Accepted Manuscripts are published online shortly after
www.rsc.org/chemicalscience
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 2041-6539
EDGE ARTICLE
Francesco Ricci et al.
Electronic control of DNA-based nanoswitches and nanodevices
rsc.li/chemical-science

Page 1 of 10
Chemical Science
View Article Online
DOI: 10.1039/C8SC03525C

Please do not adjust margins
Chemical Science
Page 2 of 10
View Article Online
DOI: 10.1039/C8SC03525C
Journal Name
COMMUNICATION
Direct synthesis of aryl‐annulated [c]carbazoles by gold(I)‐
catalysed cascade reaction of azide‐diynes and arenes†
Yuiki Kawada,a,‡ Shunsuke Ohmura,a,‡ Misaki Kobayashi,a Wataru Nojo,b Masaki Kondo,c,d Yuka
Matsuda,a Junpei Matsuoka,a Shinsuke Inuki,a Shinya Oishi,a Chao Wang,c,d Tatsuo Saito,c
Masanobu Uchiyama,*c,d Takanori Suzuki,*b and Hiroaki Ohno*a
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
The gold‐catalysed annulation of conjugated alkynes bearing an
azido group with arenes gave annulated [c]carbazoles. Using
benzene, pyrrole, and indole derivatives as the nucleophile,
benzo[c]‐, pyrrolo[2,3‐c]‐, and indolo[2,3‐c]carbazoles were
produced, respectively. The reaction proceeded through pyrrole
and benzene ring construction accompanied by the formation of
two carbon‐carbon and one carbon‐nitrogen bonds and the
cleavage of two aromatic C‐H bonds. The mechanism of the
reaction with pyrrole was investigated by density functional theory
calculations. An N,N’‐dimethylated indolo[2,3‐c]carbazole showed
dual ultraviolet‐visible‐near‐infrared and fluorescence spectra
changes upon electrolysis.
R'
O
Ar
R
N
H
N
N
H
H
aryl-annulated
[c]carbazoles
eustifoline-D
benzo[c]carbazoles
O
Br
Ar
Ar
( )2
H
N
Ar
O
O
N
HN
HO
HO
Ar
N
NaO3SO
H
OH
N
H
N
N
H
H
dictyodendrin B
Ar = C6H4(4-OH)
arcyriaflavin A
asteropusazole A
Fig. 1 Aryl‐annulated [c]carbazoles.
Introduction
Carbazoles are an important structural motif that is found in a
variety of organic molecules of current interest (Fig. 1).1
Benzo[c]carbazoles are commonly used in organic light‐emitting
diodes (OLEDs) owing to their charge‐transport properties and
thermal stability.2 Heteroaryl‐annulated [c]carbazoles are core
structures of various bioactive natural products, such as
(A) pyrrole ring formation
X
Y
Pd, Cu, Rh, etc.
+
N/Z
N/Z
stepwise or one-pot
N
H
X, Y, Z = halogen, metal, H, etc.; N = nitrogen functional group
eustifoline‐D (furo[2,3‐c]carbazole), arcyriaflavin
A
and
(B) benzene ring formation
dictyodendrins (pyrrolo[c]carbazole), and asteropusazole A
(indolo[3,2‐c]carbazole).1a Thus, the development of efficient
synthetic methods for preparing benzo[c]carbazoles and their
heteroaromatic congeners from readily accessible starting
materials is an active pursuit in organic chemistry.
[O], Pd, In, Au
etc.
ꞏ
etc.
N
H
N
N
H
H
this work
(C)
: pyrrole and benzene ring formation
cat. Au(I)
Ar
Ar
R
+
R
cascade cyclization
a Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo‐ku, Kyoto
606‐8501 (Japan).
N
H
H
H
N3
formation of 3 bonds & 2 rings
cleavage of 2 C-H bonds
b Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060‐
0810, Japan
Scheme 1 General synthetic approaches to carbazoles including aryl‐
annulated carbazoles and this work
c Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7‐3‐1
Hongo, Bunkyo‐ku, Tokyo 113‐0033, Japan
d Cluster of Pioneering Research (CPR), Advanced Elements Chemistry Laboratory,
RIKEN, 2‐1 Hirosawa, Wako, Saitama 351‐0198, Japan.
† Electronic Supplementary Informaꢀon (ESI) available: Experimental details and
spectral data are provided. CCDC 1860899 (6aF‐Me2), 1860901 (7aF‐Me2) and
1860904 (11D‐Me2). See DOI: 10.1039/x0xx00000x
The general synthetic approaches to carbazoles including
aryl‐annulated [c]carbazoles are shown in Scheme 1A and 1B.1a,3
Pyrrole ring formation based on a combination of carbon‐
‡Y. K. and S.O. contributed equally.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 1
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 3 of 10
COMMUNICATION
Journal Name
nitrogen and carbon‐carbon bond formation provides an produce 3‐substituted indoles. We envisaged that incorporating
View Article Online
efficient route to carbazoles (Scheme 1A).4,5 Reliable coupling gold carbenoid chemistry to the diyne cycDliOsaI:t1io0.n10w39o/uCl8dSCp0ro35v2id5Ce
reactions such as the Suzuki‐Miyaura, Buchwald, and oxidative direct access to aryl‐annulated [c]carbazoles (Scheme 3). Thus,
coupling reactions can be employed for this purpose. Benzene gold(I)‐mediated nucleophilic attack of the azido group of diyne
ring formation using vinyl‐ or aryl‐substituted indoles including
Diels‐Alder‐type reactions,6 hydroarylation,7 and related would produce gold carbenoid species
reactions8 leads to various carbazoles including aryl‐annulated aromatic substitution of benzene‐type arenes with
carbazoles (Scheme 1B). However, the double cyclisation produce the intermediate . Finally, the intramolecular
approach for synthesising aryl‐annulated [c]carbazoles has not hydroarylation toward alkynes18 would occur to produce the
been investigated until recently.9‐11 We expected that the gold benzo[c]carbazole
. The challenge of this strategy is controlling
1
to the proximal alkyne followed by elimination of nitrogen
. The electrophilic
would
A
A
2
3
carbenoid‐based cascade cyclisation of conjugated diynes the regioselectivity when using pyrrole‐type heteroarenes as
would directly provide aryl‐annulated [c]carbazoles in a single the coupling partner: whereas the first nucleophilic attack at the
operation via the sequential cleavage of two aromatic C‐H pyrrole 3 position would produce pyrrolo[2,3‐c]carbazole
bonds (Scheme 1C). first nucleophilic attack at the pyrrole 2 position would give
Homogenous gold catalysis has emerged as a powerful tool pyrrolo[3,2‐c]carbazole through 3‐pyrrolylindole
for atom‐economical transformations.12 The π‐acidity of gold intermediates
and , respectively. Attention should also be
catalysts enables the acꢀvaꢀon of C−C mulꢀple bonds to given to the regioselectivity in the second arylation in the
6, the
7
,
4
5
promote various transformations. Recent investigations using reaction with the benzene‐type nucleophile (
diynes in gold‐catalysed reactions have revealed that both
2
to
3
).
R'
conjugated and unconjugated diynes are useful precursors of
R'
R
R
complex molecules.13 For example, we recently reported a gold‐
N3
catalysed formal [4 + 2] reaction between 1,3‐diynes and
1
N
H
R
N
H
pyrroles for synthesising 4,7‐disubstituted indoles (Scheme 2A,
n = 0).14a This reaction proceeded through a double
hydroarylation cascade involving the initial intermolecular
hydroarylation of a 1,3‐diyne at the 2‐position of a pyrrole,
followed by an intramolecular hydroarylation. When using
skipped diynes as the substrates, the formal [5 + 2] reaction
cat. Au(I)
2
3
6
R'
[Au+]
NR''
NR''
R
N
R
A
N
H
N
H
R
R
4
N
R''
efficiently
proceeded
to
produce
1,6‐
R''N
R''N
dihydrocyclohepta[b]pyrrole derivatives,14b which can be
considered as homologs of 4,7‐disubstituted indoles (Scheme
2A, n = 1).
R
N
H
5
N
H
7
Scheme 3 Possible reaction pathways
(A) gold-catalyzed formal [4 + 2] and [5 + 2] reactions of diynes (our group)
R
R
R
R
Herein, we report a full account of our study on the direct
synthesis of aryl‐annulated [c]carbazoles by regioselective gold‐
catalysed annulation of conjugated diynes and arenes such as
benzene, pyrrole, and indole derivatives.19 Computational
investigations for elucidating the mechanism as well as redox
and fluorescence properties of the pyrrolo[2,3‐c]carbazoles are
also presented.
6-endo
or
7-endo
[Au+]
( )n
( )n
cat. Au(I)
( )n
[Au+]
hydroarylation
( )n
N
H
R
N
N
H
H
R
R
(n = 0 or 1)
hydroarylation
(n = 0 or 1)
(B) indole synthesis via gold carbenoid formation (Zhang, Gagosz)
R
[Au]
[Au+]
Nu
cat. Au(I)
NuH
R
N
R
R
Results and discussion
N3
N
N
N2
H
N2
Reaction with benzene derivatives. The azido‐substituted
(NuH = ROH or ArH)
diynes
1 were easily prepared through Cadiot–Chodkiewicz
Scheme 2 Related works
coupling20 between 2‐ethynyaniline and bromoalkynes
(Scheme 4). The resulting anilines bearing a conjugated diyne
We then turned our attention to synthesising aryl‐annulated
[c]carbazole based on gold‐carbenoid formation15 using
conjugated diynes. In 2011, Gagosz16a and Zhang16b
independently reported the gold(I)‐catalysed synthesis of
indoles bearing an electron‐donating group at the 3‐position
(Scheme 2B).17 The reaction can be rationalised by the
formation of a gold carbenoid intermediate followed by
nucleophilic reaction at the carbenoid moiety. As the coupling
partner, alcohol and arenes can be used for the reaction to
moiety were converted to 1a–g via the Sandmeyer reaction with
sodium azide (see Supplementary Information).
Ar
Ar
1) NaNO2
Ar
Br
conc. HCl
CuCl
NH2OHꞏHCl
2) NaN3
NH2
NH2
N3
1a
g
–
Scheme 4 Preparation of azide‐diynes
2 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Chemical Science
Please do not adjust margins
Page 4 of 10
Journal Name
COMMUNICATION
We initially screened a variety of different gold catalysts (5 140 °C improved the yield to 86% (entry 12), whereas the
View Article Online
DOI: 10.1039/C8SC03525C
mol %) for the synthesis of benzo[c]carbazole using diyne 1a reaction at 80 °C did not reach completion (entry 11). Thus, we
and anisole 8A (10 equiv.) (Table 1, entries 1–5). Ph3PAuSbF6 in used the conditions shown in entry 10 (10 equiv. of arene,
1,2‐dichloroethane (DCE) did not promote even the first condition A) and entry 12 (arene as the solvent, condition B) for
arylation of the desired transformation (entry 1). IPr, XPhos, and further investigations for benzo[c]carbazole synthesis.
BrettPhos (Fig. 2) were ineffective ligands for bis‐cyclisation;
OMe
however, the 3‐phenylindole intermediate 2aA was formed in
36–65% yields (entries 2–4). Fortunately, the annulation
reaction was promoted by JohnPhosAu(MeCN)SbF6 (entry 5) to
provide the desired fused carbazole 3aA in 44% yield. Next, we
examined the choice of reaction solvent using
JohnPhosAu(MeCN)SbF6 as the catalyst. The reaction using
benzene, propan‐2‐ol, and 1,4‐dioxane gave the
monocyclisation product 2aA (63–87% yields) without forming
the carbazole 3aA (entries 6–8). Carrying out the reaction in
1,1,2,2‐tetrachloroethane (TCE) at 140 °C increased the yield of
3aA to 55% (entry 9). In this case, decomposition of
JohnPhosAu(MeCN)SbF6 at high reaction temperature was
anticipated. Thus, the first arylation was conducted at 80 °C and,
after the disappearance of starting material and formation of
2aA (monitored by TLC), the reaction temperature was raised to
140 °C for the second arylation, giving rise to higher yield of the
fused carbazole 3aA (75% yield, entry 10). Finally, examination
of the stoichiometry revealed that the reaction using excess
anisole (as solvent) and 5 mol % BrettPhosAu(MeCN)SbF6 at
i-Pr
i-Pr
PCy2
MeO
PCy2
P(t-Bu)2
N
N
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
BrettPhos
IPr
XPhos
JohnPhos
Fig. 2 Structures of screened ligands.
Using these optimised reaction conditions, we then
explored the scope of the reaction. Variation of the substitution
on the aryl moiety of the nucleophile
8
was initially investigated
8B and 1,3‐
(Table 2). 1,2‐Dimethoxybenzene
(
)
dimethoxybenzene (8C) served as suitable nucleophiles for the
gold‐catalysed annulation when used as the solvent (condition
B), to give the benzo[c]carbazoles 3aB (quant) and 3aC (95%) in
excellent yields. In these cases, the reaction using 10 equiv. of
nucleophile (condition A) also permitted 70% and 40% yields of
3aB and 3aC, respectively. The reaction with benzodioxole (8D
afforded pentacyclic benzo[c]carbazole (3aD) in 76% yield. Less
)
Table 1. Reaction optimization using anisole a
OMe
OMe
Ph
cat. Au(I) (5 mol %)
+
OMe
+
Ph
N3
1a
N
N
Ph
H
H
8A
3aA
2aA
Yield d (%)
3aA
Entry
Catalyst b
Solvent c
Temperature (time)
2aA
0
1
2
Ph3PAuCl/AgSbF6
IPrAuNTf2
DCE
DCE
80 °C (44 h)
80 °C (24 h)
0
0
36
57
65
26
78
63
87
0
3
XPhosAuCl/AgNTf2
DCE
80 °C (21 h)
0
4
BrettPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
JohnPhosAu(MeCN)SbF6
BrettPhosAu(MeCN)SbF6
BrettPhosAu(MeCN)SbF6
DCE
80 °C (30 h)
0
5
DCE
80 °C (26 h)
44
0
6
benzene
propan‐2‐ol
1,4‐dioxane
TCE
80 °C (10 h)
7
80 °C (10 h)
0
8
80 °C (10 h)
0
9
140 °C (13 h)
80 °C (1 h), 140 °C (16 h)
80 °C (15 h)
55
75
13
86
10
11
12
TCE (condition A)
anisole
0
28
0
anisole (condition B)
140 °C (19.5 h)
a
b
Reactions were carried out using 1a (1 equiv.), 8A (10 equiv.), gold catalyst (5 mol %). The ligand structures are shown in Fig. 2. BrettPhosAu(MeCN)SbF6,
JohnPhosAu(MeCN)SbF6, and IPrAuNTf2 were prepared in advance. The other catalysts were prepared in‐situ by mixing AuCl∙ligand with AgNTf2 or AgSbF6. c DCE =
1,2‐dichloroethane, TCE = 1,1,2,2‐tetrachloroethane. d Isolated yields.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 3
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 5 of 10
COMMUNICATION
Journal Name
nucleophilic o‐xylene (8E) also gave the corresponding of NH‐pyrrole than that of the C3 position.22 Expecting that the
View Article Online
DOI: 10.1039/C8SC03525C
benzo[c]carbazole (3aE) in moderate yield (42%), although an regioselectivity of nucleophilic attack could be controlled by
increased loading of the gold catalyst (20 mol %) was required. steric and electronic factors of the pyrrole, we subsequently
Benzene and toluene did not provide the fused carbazoles evaluated the impact of substitution at the pyrrole nitrogen
owing to their lower reactivities. In all cases using arenes 8A
–
E,
(entries 2–6). As expected, regioselectivity was significantly
the cascade reaction proceeded in a regioselective manner: the affected by the N‐substituent: N‐Boc pyrrole 9F showed the
first arylation occurred at the para‐position of the electron‐ highest regioselectivity to produce the pyrrolo[2,3‐c]carbazole
donating substituent of
occurred at the less‐sterically‐hindered carbon of the preferentially produced the corresponding [3,2‐c]‐isomer 7aB
introduced aryl group. We next investigated the reaction using = 18:82, entry 2).
various diynes 1b
under condition B.21 A methyl substituent
8, and the second hydroarylation 6aF (6:7 = 92:8, entry 6), whereas N‐benzylpyrrole 9B
(6:7
–
g
Table 3. Optimisation of pyrrole structure a
at the ortho‐, meta‐, or para‐ position of the terminal phenyl
Ph
group was tolerated, producing the corresponding
RN
NR
Ph
benzo[c]carbazoles (3bA
94%). Similarly, the reaction of 1e
donating or ‐withdrawing group (Cl, NO2, or OMe) at the para
position gave the desired products 3eA 3gA (43–74% yield).
–
3dA) in good to excellent yields (70–
cat. Au(I)
+
Ph
–
g
bearing an electron‐
N
N
N3
1a
H
H
N
R
9A
F
6aA
F
7aA F
–
–
–
–
The lower yield of the nitro derivative 3fA can be attributed to
the less efficient coordinating ability of the electron‐deficient
alkyne(s) to the gold catalyst, which would decrease the
probability of being activated.
Time
(h)
Yield b
(%)
Ratio c
Entry
Pyrrole
R
(6 : 7)
25 : 75
18 : 82
58 : 42
81 : 19
82 : 18f
92 : 8
1
2
3e
9A
9B
9C
9D
9E
9F
H
Bn
Ts
8
<62%d
62%
34%
62%
60%
60%
10
Table 2 Scope of benzo[c]carbazole synthesis a
0.5
1.5
1.5
1.5
4
CO2Me
Piv
BrettPhosAu(MeCN)SbF6
Ar
(5 mol %)
R'
Ar
5
8
8
conditions A (10 equiv.
or conditions B (excess
)
)
6
Boc
R'
N
a Reaction conditions: 9 (5 equiv.), BrettPhosAu(MeCN)SbF6 (5 mol %), DCE, 80 °C.
N3
H
b
c
d
Combined isolated yields. Determined by 1H NMR spectroscopy. Contained
1a–g
3
8A E
–
small amounts of impurities. e Reaction carried out in TCE at 140 °C using 10 mol %
f
of the catalyst. Separation of the minor isomer from other by‐products was
O
MeO
O
OMe
Ph
OMe
difficult.
MeO
The structural elucidation of 6aF and 7aF was
unambiguously made by X‐ray crystallographic analyses of the
methylation products 6aF‐Me2 and 7aF‐Me2 (Fig. 3). The
pyrrolocarbazole moiety adopted a planer geometry as
expected, and the twist angle of the phenyl group was 71.1° (for
6aF‐Me2) or 26.2–44.0° (for 7aF‐Me2).23 The larger twist angle
of the phenyl group in 6aF‐Me2 was attributed to the presence
of an N‐methyl group in close proximity to the phenyl group.
Ph
Ph
N
H
N
N
H
H
3aC
3aD
3aB
40% (A, 2 + 15 h)
95% (B, 26 h)
76% (B, 18 h)
70% (A, 2 + 15 h)
quant (B, 27 h)
Me
Me
OMe
OMe
2'
3'
Me
4'
Ph
X
N
H
N
N
H
H
MeN
3aE
NMe
3bA (2'-Me) 89% (B, 20 h)
3eA (X = Cl)
74% (B, 22.5 h)
43% (B, 20 h)
61% (B, 12 h)
1) HCl/dioxane
80 °C
42% (B, 1 h)b
(3'-Me)
(4'-Me)
(X = NO2)
3cA
3dA
94% (B, 20 h)
70% (B, 23 h)
3fA
3gA
6aF
7aF
+
(X = OMe)
+
Ph
Ph
2) NaH, MeI, DMF
0 °C to rt
N
Me
N
Me
a
Reaction conditions: 1a, 8 (excess), and gold catalyst (5 mol %). The reaction
38% (2 steps)
6aF-Me2
7aF-Me2
conditions employed (condition A or B) and reaction time are shown in
parentheses. b Catalyst loading was increased to 20 mol %.
Reaction with pyrrole and indole derivatives. Next, we
investigated the synthesis of pyrrolocarbazoles by the reaction
with pyrroles
9 (Table 3). The gold‐catalysed reaction of
6aF-Me2
7aF-Me2
conjugated diyne 1a with NH‐pyrrole 9A produced an isomeric
mixture of the two annulation products 6aA and 7aA in ca. 62%
yield, along with several unidentified minor products (entry 1).
In this case, the pyrrolo[3,2‐c]carbazole 7aA was obtained as
Fig. 3 Synthesis and X‐ray structures of dimethylated pyrrolocarbazoles.
The phenyl group in the latter adopted two orientations in the crystal
structure.
the major isomer (6aA:7aA = 25:75). This result can be readily
understood by the more nucleophilic nature of the C2 position
4 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Chemical Science
Please do not adjust margins
Page 6 of 10
Journal Name
We then optimised the reaction conditions for efficiently produced (
pyrrolocarbazole formation using diyne 1a, N‐Boc‐pyrrole 9F (5 slightly decreased when using electron‐deficient diyne 1f
equiv.), and various gold catalysts (5 mol %) (Table 4). Whereas substituted by a nitro group. Diynes 1h and 1i substituted by a
Ph3PAuCl/AgNTf2 showed low reactivity (<5% yield, entry 1), cyano or methoxy group at the para‐position to the azido group
COMMUNICATION
6:
7
= 95:5). The regioseVleiecwtAivrtiitcyle Ownlianse
DOI: 10.1039/C8SC03525C
other gold complexes bearing IPr, JohnPhos, XPhos, or also showed relatively low selectivities (
BrettPhos as the ligand resulted in formation of the pyrrolo[2,3‐
c]carbazole 6aF in sufficient regioselectivities (>91:9) and
6
:
7
= 81:19‐91:9).
Table 5 Scope of pyrrolo[2,3‐c]carbazole synthesis a
Ar
moderate yields (55–62%, entries 2–5). Using the most efficient
ligand BrettPhos in terms of regioselectivity (6:7 = 94:6, entry 5),
two other silver salts were tested (AgSbF6 and AgOTf, entries 6
and 7, respectively); however, the regioselectivity was not
improved. The use of a gold complex prepared in advance
slightly improved the reactivity (reaction completed within 0.5
BocN
NBoc
R
R
Au(I) (5 mol %)
condition C
R
+
Ar
Ar
N
H
N
H
7
N3
1b
N
Boc
i
9F
6
–
NBoc
NBoc
h) and regioselectivity (6:7 = 95:5, entries 8, 9). The solvent
2'
3'
Me
4'
screening and investigations of reaction temperature did not
improved the yields and product ratio (see Supplementary
Information), whereas the reaction at 80 °C was found to be
acceptable (entry 10). From these results, we used the
conditions shown in entry 8 (condition C) and entry 10
(condition D) for further studies.
X
N
H
N
H
6eF
6 7
: = 95:5 (0.5 h)
6fF (X = NO2) 64%, 6:7 = 91:9 (1.5 h)
6gF (X = OMe) 67%, 6:7 = 95:5 (0.5 h)
6bF (2'-Me) 58%, 6:7 = 95:5 (0.5 h)
(X = Cl)
65%,
6cF
6dF
6 7
6 7
(3'-Me) 55%,
(4'-Me) 57%,
:
:
= 95:5 (0.5 h)
= 95:5 (0.5 h)
NBoc
MeO
NBoc
NC
Table 4. Reaction optimisation using N‐Boc‐pyrrole a
N
H
N
H
6iF
6 7
: = 91:9 (0.5 h)
52%,
6hF
6 7
: = 81:19 (1 h)
61%,
Ph
BocN
NBoc
a Reaction conditions: 9F (5 equiv.), BrettPhosAu(MeCN)SbF6 (5 mol%), TCE, 110 °C
Au(I) (5 mol %)
+
Ph
Ph
(condition C).
N
H
N
H
N3
1a
N
Boc 9F
6aF
7aF
We then applied indole derivatives as the nucleophile for
the annulation reaction (Table 6). The reactions of azide‐diyne
Time
(h)
Yield b
(%)
Ratio c
(6:7)
1a with N‐protected indoles 10A
under condition C regioselectively gave the indolo[2,3‐
c]carbazoles 11A as well as several unidentified by‐products.
–C
(R1 = Boc, Piv, or CO2Et)
Entry
Catalyst
–C
1
2
3
4
5
6
7
Ph3PAuCl/AgNTf2
IPrAuCl/AgNTf2
24
1
<5d
60
87 : 13
91 : 9
92 : 8
93 : 7
94 : 6
89 : 11
75 : 25
The structure of 11A was confirmed by X‐ray analysis after
cleavage of the N‐Boc group and dimethylation,24 similarly to
the cases of 6aF and 7aF (Fig. 3). Indoles possess reactive sites
other than the desired 2‐ and 3‐positions, which may cause
undesired side reactions.16b Thus, the introduction of an
electron‐withdrawing group at the 5‐position of indole was
JohnPhosAuCl/AgNTf2
XPhosAuCl/AgNTf2
BrettPhosAuCl/AgNTf2
BrettPhosAuCl/AgSbF6
BrettPhosAuCl/AgOTf
1
56
1
62
1
55
3
51
examined. As expected, indoles 10D
–F bearing a bromo, chloro,
or ethoxycarbonyl group at the 5‐position reacted more
20
<12d
efficiently to afford the indolo[2,3‐c]carbazoles 11D
yields (50–67%) under condition D.
–F
in better
BrettPhosAu(MeCN)SbF6,
(TCE, 110 °C: condition C)
8
0.5
58
95 : 5
Table 6 Scope of indolo[2,3‐c]carbazole synthesis a
9
BrettPhosAuNTf2
0.5
1.5
58
60
95 : 5
92 : 8
R2
BrettPhosAu(MeCN)SbF6
10
(DCE, 80 °C: condition D)e
Ph
R2
NR1
Ph
Au(I) (5 mol %)
condition C
a Reaction conditions: 9F (5 equiv.), gold catalyst (5 mol %), TCE, 110 °C. b Combined
isolated yields. c Determined by 1H NMR spectroscopy. d Contained small amounts
of impurities. e The reaction was conducted in DCE at 80 °C.
5
+
N
N
N3
1a
R1
H
10A–F
11A
F
–
We subsequently investigated the scope of the pyrrolo[2,3‐
c]carbazole formation (Table 5). The conjugated diynes 1b–i
R2
bearing electron‐donating or ‐withdrawing substituents on both
the aryl groups reacted smoothly with pyrrole 9F to afford the
corresponding carbazoles 6bF–6iF under condition C. The
position of a methyl group or introduction of chloro or methoxy
substituents to the terminal aryl group did not significantly
affect the reaction, and the desired annulation products were
NR1
Ph
NCO2Et
Ph
N
N
H
H
(R1 = Boc)
(R1 = Piv)
35% (C, 3 h)
12% (C, 6.5 h)
44% (C, 6.5 h)
(R2 = Br)
11D
50% (D, 4.5 h)
52% (D, 4.5 h)
11A
11B
11C
11E (R2 = Cl)
(R1 = CO2Et)
(R2 = CO2Et) <67% (D, 7.5 h)b
11F
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 5
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 7 of 10
COMMUNICATION
Journal Name
a
Reaction conditions: 10 (5 equiv.), BrettPhosAu(MeCN)SbF6 (5 mol%). The
pyrrole 9F was a slightly more efficient partner in the first
View Article Online
reaction conditions employed (condition C or D) and reaction time are shown in
parentheses. b Contained small amounts of impurities.
arylation than anisole 8A, and thatDOthI:e10.1a0n3i9s/oCl8eS‐Cd0e3r5iv2e5Cd
intermediate 2aA was significantly less reactive for the second
arylation than the pyrrole‐derived intermediate. The
competition reaction using dimethoxybenzene 8B and N‐Boc‐
pyrrole 9F gave the biscyclisation products 3aB (37%) and 6aF
(34%) in comparable yields (eq 3 in Scheme 6). This result
suggested that the second arylation was accelerated by the
additional methoxy group located at the para position to the
reacting carbon.26 We then examined the kinetic isotope effect
(eq 4 in Scheme 6). The competition reaction using N‐Boc‐
pyrroles 9F (2.5 equiv.) and 9F‐d4 (2.5 equiv.) under condition C
gave the corresponding pyrrolocarbazoles 6aF and 7aF, where
the D/H ratios were 1:1 in both products. Thus, deprotonation
was not the rate‐determining step for formation of these
products. This result suggested that electrophilic aromatic
substitution was more likely for the first arylation than C‐H
insertion.27
Reaction mechanism. Although nucleophilicity of arenes
including heteroarenes were well investigated previously, their
relative reactivity between N‐Boc‐pyrrole is not well
understood.25 To better understand the reaction mechanism as
well as relative reactivities of arenes employed in this study,
several further experiments were performed. First, the
exposure of 2aA (obtained during the reaction optimisations
shown in Table 1) to the gold‐catalysed reaction conditions led
to its complete conversion to the corresponding
benzo[c]carbazole 3aA in 90% yield (Scheme 5). Second, the
reaction of 1a with the pyrrole 9F was intentionally stopped
before it reached completion, which afforded the alkyne‐
substituted indoles 4aF and 5aF in 25% yield (4:5 = 69:31) along
with the recovered starting material. These alkynylindoles were
consumed completely under the gold‐catalysed reaction
conditions to produce the pyrrolocarbazoles 6aF and 7aF in 67%
and 82% yield, respectively. These results strongly indicated
that the reactions proceeded through stepwise nucleophilic
attack of the arenes to the gold carbenoid followed by
intramolecular hydroarylation, as per our intended reaction
pathway.
OMe/Me
OMe
OMe
Me
8A
8F
(1)
+
1a
Ph
condition A
80 °C, 2 h
then 140 °C, 16 h
N
H
Ph
N
H
3aB
2aA
2aF
(OMe, 30%)
(Me, 2%)
(29%)
OMe
OMe
OMe
N
OMe
NBoc
Ph
Boc
9F
8A
condition C'
+
(2)
1a
BrettPhosAu(MeCN)SbF6 (5 mol %)
N
H
2aA
N
H
6aF
Ph
Ph
0.5 h
TCE, 140 °C, 23 h
N
N
H
3aA
Ph
Ph
(27%)
(41%)
H
2aA
(90%)
OMe
OMe
MeO
OMe
BocN
N
N
Boc
NBoc
NBoc
Ph
Boc
8B
9F
9F
+
1a
(3)
+
Ph
condition C'
0.5 h
(a)
N
Ph
N
H
Ph
N
H
3aB
N
H
6aF
N3
1a
H
4aF
69:31
(25%)
5aF
(37%)
(34%)
D
D
D
(b)
(b)
D H
D H
/
/
BocN
D/H
D
NBoc
Ph
N
Boc
9F
N
BocN
D H
/
NBoc
Boc
9F
-d4
Ph
1a
+
(4)
Ph
Ph
N
N
H
7aF
condition C
0.5 h
H
N
H
N
H
6aF
(67%)
(82%)
6aF-D H
7aF-D H
/
/
88:12 (59%)
D H
/
= 1:1
Scheme 5 Hydroarylation of the monocyclisation Intermediates. Reaction
conditions: (a) 9F (5 equiv.), BrettPhosAu(MeCN)SbF6 (5 mol%), DCE, 60 °C, 1.5 h.
(b) BrettPhosAu(MeCN)SbF6 (5 mol%), TCE, 110 °C, 0.5 h.
Scheme 6 Competition experiments between different nucleophiles.
Condition A: nucleophiles (5 equiv. each), JohnPhosAu(MeCN)SbF6 (10
mol%), TCE, 80 °C then 140 °C. Condition C/C’: nucleophiles (2.5 equiv. each
for condition C; 5 equiv. each for condition C’), BrettPhosAu(MeCN)SbF6 (5
mol%), TCE, 110 °C.
Competition experiments using two different arenes were
then carried out (Scheme 6). The gold‐catalysed reaction of 1a
with anisole 8A (5 equiv.) and toluene 8F (5 equiv.) under
condition A gave the anisole‐derived products 2aA (30%) and
3aB (29%) along with a small amount of the toluene derivative
2aF (2%) (eq 1 in Scheme 6). Thus, the first arylation was highly
dependent on the nucleophilicity of the arene.25 The
competition between anisole 8A (5 equiv.) and N‐Boc‐pyrrole
9F (5 equiv.) led to formation of the anisole‐derived
monocyclised product 2aA (27%) and pyrrole‐derived
biscyclised product 6aF (41%), the latter being the preferred
product (eq 2 in Scheme 6). This result suggested that N‐Boc‐
To further elucidate the reaction mechanism, we undertook
density functional theory (DFT) calculations. The calculations
were conducted at the M06L/6‐31G** (for H, C, N, and P) and
SDD (for Au) levels using the formation of pyrrolo[2,3‐
c]carbazole from 1a and N‐methylpyrrole as the model reaction
(Fig. 4A). As previously proposed,16 the reaction initiates by
intramolecular nucleophilic attack of the azide group to the
activated alkyne through TS1/2 to form an indolyl‐gold
6 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Chemical Science
Please do not adjust margins
Page 8 of 10
Journal Name
COMMUNICATION
View Article Online
DOI: 10.1039/C8SC03525C
(A)
･+
･+
AuPMe3
AuPMe3
AuPMe3
AuPMe3
–0.4
+10.9
+2.3
Ph
Ph
Ph
Ph
Ph
Ph
･ –
–32.5
N
N
N2･+
INT1
TS1/2
INT2
TS2/3
N
N2･+
N3
N2
･ +
NMe
–N2
NMe
NMe
AuPMe3
･+
NMe
AuPMe3
AuPMe3
AuPMe3
H
+13.1
+1.4
Ph
Ph
Ph
–20.3
–12.2
N
N
N
N
–47.9
INT4
TS3/4
INT3-2
INT3-1
NMe
MeN
NMe
NMe
INT5-2
TS5/6
H
H
AuPMe3
H+
+11.2
Ph
Ph
Ph
–29.7
–15.2
N
N
Me3PAu
N
N
H
TS4/5
INT5-1
AuPMe3
AuPMe3
H
MeN
MeN
Calculation Method:
M06L/6-31G** (for H, C, N, P) and SDD (for Au)
H
PD
INT6
Ph
H+
+6.2
AuPMe3
Ph
Ph
Energy Level:
G (Gibbs Free Energy, kcal/mol)
SM
AuPMe3
N3
H
N
H
N
H
–26.1
(B)
G (kcal/mol)
20.0
TS2/3
TS1/2
INT2
0.0
INT1
-20.0
-40.0
TS3/4
INT3-1
TS4/5
INT3-2
-60.0
INT4
-80.0
TS5/6
INT5-1
-100.0
-120.0
INT5-2
PD
INT6
Fig. 4 DFT calculations for cyclisation of 1a with N‐methylpyrrole [M06L/6‐31G**(H, C, N, P)&SDD(Au)].
intermediate INT2 with a small barrier of 10.9 kcal/mol and a C–C bonds, and the formation of two aromatic rings. This
rather large endothermicity (10.5 kcal/mol higher than INT1). provides the driving force for the overall reaction.
This unfavourable energy loss is compensated for by successive
reaction(s). INT2 ejects nitrogen to form a gold carbenoid
intermediate INT3‐1 with a large stabilisation energy (45.6 From the viewpoint of electronic structure, pyrrolo[2,3‐
kcal/mol). Next, the key arylation step occurs by intermolecular c]carbazoles and indolo[2,3‐c]carbazoles 11 could be
nucleophilic attack of N‐methylpyrrole to the gold carbenoid considered as ‐fused 1,4‐phenylenediamines. Thus, their
INT3‐2 through TS3/4, with a small barrier of 1.4 kcal/mol, to cation radicals would be generated as persistent species as the
produce INT4. The gold rearrangement from C to N, with a
‐extended form9c‐e,28 of Wurster's Blue.29 According to
Electrochemical investigations of pyrrolo[2,3‐c]carbazoles.
6


reasonable barrier of 16.6 kcal/mol, gives an N‐aurated indole voltammetric analyses in CH2Cl2 (Table 7), the oxidation process
intermediate INT5‐1. This occurs with the simultaneous re‐ of pyrrolo[2,3‐c]carbazole 6aF‐H was irreversible as in the
aromatisation, protodeauration, and re‐complexation of the isomer, pyrrolo[3,2‐c]carbazole 7aF‐H. Substitution with methyl
gold catalyst with the internal acetylene, and exothermically groups at the reactive position (N‐H of pyrrole) failed to stabilise
provides the pyrrole‐substituted indole intermediate INT5‐2
.
the cation radical species, as shown by the irreversible oxidation
Finally, 6‐endo‐dig cyclisation of INT5‐2 is promoted by the gold wave for 6aF‐Me2. This was despite the electron‐donating
catalyst to produce the pyrrolo[2,3‐c]carbazole (PD), which nature of the substituents marginally facilitating the
regenerates the active gold catalyst. The entire reaction profile electrochemical oxidation, as indicated by the less positive
is illustrated in Fig. 4B. All the transition states have reasonable oxidation potentials. By fusing the benzene nucleus in 6aF‐Me2
energy barriers (1.4–13.1 kcal/mol). The overall exothermicity to furnish the indolo[2,3‐c]carbazole skeleton, the cation radical
is very large because of the formation of one C–N bond and two species could attain enough persistency. 11A‐Me2 underwent
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 7
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 9 of 10
COMMUNICATION
Journal Name
reversible two‐stage one‐electron oxidation processes, as gives rise to fluorescence properties,30 so the eVleiecwtArrotilcylesOisnlionef
DOI: 10.1039/C8SC03525C
shown by the voltammogram (Fig. 5). The redox pathway can be 11A‐Me2 also caused a change in the fluorescence (FL) spectrum
postulated as shown in the scheme, similar to that for 1,4‐
phenylenediamine.
[em 424, 442 (sh) nm in CH2Cl2 (ex 354 nm)]. The steady
decrease in fluorescence with increasing electrochemical
oxidation time could be rationalised by the non‐fluorescent
nature of its cation radical. Such dual electrochromism in which
changes occur in both UV‐Vis‐NIR and FL spectra is rare,30 but
was also realised in our previous study on benzo[g]indolo[2,3‐
c]carbazole derivatives,9c‐e which were synthesised through a
different mode of the gold(I)‐catalysed cascade reaction.9a Thus,
the gold‐catalysed synthesis of annulated carbazoles is a
powerful tool for exploring the little developed category of
advanced electrochromic systems.
Table 7. Oxidation potentials of pyrrolocarbazoles a
RN
NMe
Ph
NR
Ph
Ph
N
N
N
Me
R
R
11A-Me2
6
7
Entry
Compound
6aF‐H
R
H
Oxidation potential a
1
2
3
4
5
+0.85
+0.79
+0.73
+0.75
+0.80 b
6aF‐Me2
7aF‐H
Me
H
7aF‐Me2
11A‐Me2
Me
–
a E/V vs SCE, CH2Cl2 containing 0.1 M Bu4NPF6, Pt electrode, 100 mV s‒1. Eox = Epa
–
0.03 V (for entries 1–5). E(Fc/Fc+) = +0.53 V under similar conditions. b Reversible
redox reaction was observed.
Ph
Ph
Ph
e
e
e
e
MeN
NMe
MeN
NMe
MeN
NMe
Fig. 6 Continuous changes in UV‐Vis‐NIR (upper panel) and fluorescence
(lower panel) spectra upon constant current electrochemical oxidation
of 11A‐Me2 [in CH2Cl2 (7.1 × 10‒6M) containing 0.05 M Bu4NPF6 (20 µA,
every 8 min)].
+
2+
11A-Me2
11A-Me2
11A-Me2
Fig. 5 Cyclic voltammogram of 11A‐Me2 in CH2Cl2 (upper panel) and
possible redox pathway (lower panel). The irregular peak shape for the
second oxidation wave may have been related to partial adsorption of the
doubly‐charged species on the electrode.
Conclusions
We have developed a strategy for synthesising aryl‐annulated
[c]carbazoles through the gold‐catalysed cascade cyclisation of
azido‐diynes. The reaction with electron‐rich benzenes such as
anisole and toluene gave benzo[c]carbazoles via
functionalisation of two benzene C‐H bonds. Use of N‐Boc‐
pyrrole and indoles as a coupling partner regioselectively
produced the corresponding heteroaryl‐annulated carbazoles,
namely pyrrolo[2,3‐c]carbazoles and indolo[2,3‐c]carbazoles,
respectively. The reaction proceeded through intramolecular
nucleophilic attack of azide to the proximal alkyne to form a
Upon electrochemical oxidation of 11A‐Me2 in CH2Cl2, the
colourless solution turned green, which demonstrated its
electrochromic nature. A continuous change in ultraviolet‐
visible‐near‐infrared (UV‐Vis‐NIR) absorption was accompanied
by several isosbestic points, indicating that 11A‐Me2 was cleanly
oxidised into the corresponding cation radical species (Fig. 6).
Wurster's Blue exhibits absorption only in the Vis region (
700 nm). Thus, the observed red shift was induced through
 <

‐
extension by fusing of the indole rings. The carbazole skeleton
8 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Chemical Science
Please do not adjust margins
Page 10 of 10
Journal Name
COMMUNICATION
K. Tan, M. Mathiew, S. Nayak and P. W. H. ChanV,iCewheArmtic.leAOsnilainne
gold carbenoid species, nucleophilic attack of arenes to the
carbenoid, and subsequent 6‐endo‐dig cyclisation of the
introduced arene to the other alkyne. This proposed reaction
mechanism was well supported by the results of DFT
calculations, competition experiments, and deuterium‐labeling
experiments. An N,N’‐dimethylated derivative of indolo[2,3‐
c]carbazole showed dual UV‐Vis‐NIR and fluorescence spectral
changes on electrolysis, which demonstrates the potential
utility of this reaction in materials chemistry.
J., 2017, 12, 1475–1479.
DOI: 10.1039/C8SC03525C
8
9
(a) R. Y. Huang, P. T. Franke, N. Nicolaus and M. Lautens,
Tetrahedron, 2013, 69, 4395–4402; (b) P. Raju and A. K.
Mohanakrishnan, Eur. J. Org. Chem., 2016, 4361–4371.
For our studies on annulated [c]carbazoles, see: (a) K.
Hirano, Y. Inaba, K. Takasu, S. Oishi, Y. Takemoto, N. Fujii and
H. Ohno, J. Org. Chem., 2011, 76, 9068–9080; (b) M. Taguchi,
Y. Tokimizu, S. Oishi, N. Fujii and H. Ohno, Org. Lett., 2015,
17, 6250–6253; see also: (c) T. Suzuki, Y. Tokimizu, Y. Sakano,
R. Katoono, K. Fujiwara, S. Naoe, N. Fujii and H. Ohno, Chem.
Lett., 2013, 42, 1001–1003; (d) T. Suzuki, Y. Sakano, Y.
Tokimizu, Y. Miura, R. Katoono, K. Fujiwara, N. Yoshioka, N.
Fujii and H. Ohno, Chem. Asian J., 2014, 9, 1841–1846; (e) T.
Acknowledgements
Suzuki, W. Nojo, Y. Sakano, R. Katoono, Y. Ishigaki, H. Ohno
This work was supported by the JSPS KAKENHI [Grant Numbers
JP15KT0061 (HO), 18H04408 (HO), 18H04376 (TK), 17H05430
(MU), 17H06173 (MU)], the Platform Project for Supporting
Drug Discovery and Life Science Research (Platform for Drug
Discovery, Informatics, and Structural Life Science) from the
Japan Agency for Medical Research and Development (AMED),
and the Hoansha Foundation. A generous allotment of
computational resources (Projects G17022, G18008) from
HOKUSAI GreatWave (RIKEN) is gratefully acknowledged.
and K. Fujiwara, Chem. Lett., 2016, 45, 720–722.
10 Quite recently, synthesis of aryl‐annulated [c]carbazoles via
silver‐mediated amination/cyclisation/aromatisation cascade
was reported: X. Fan, L.‐Z. Yu, Y. Wei and M. Shi, Org. Lett.,
2017, 19, 4476–4479.
11 For carbazole syntheses based on rhodium‐catalysed [2 + 2 +
2] cycloisomerisation of alkynes, see: B. Witulski and C.
Alayrac, Angew. Chem. Int. Ed., 2002, 41, 3281–3284.
12 For selected reviews, see: (a) H. Ohno, Isr. J. Chem., 2013, 53
,
869 882; (b) R. Dorel and A. M. Echavarren, Chem. Rev.,
–
2015, 115, 9028–9072; (c) D. Pflästerer and A. S. K. Hashmi,
Chem. Soc. Rev., 2016, 45, 1331–1367; (d) Y. Li, W. Li and J.
Zhang, Chem. Eur. J., 2017, 23, 467–512.
Conflicts of interest
There are no conflicts to declare.
13 (a) A. M. Asiria and A. S. K. Hashmi, Chem. Soc. Rev., 2016,
45, 4471–4503; (b) S. M. Abu Sohel and R.‐S. Liu, Chem. Soc.
Rev., 2009, 38, 2269–2281.
14 (a) Y. Matsuda, S. Naoe, S. Oishi, N. Fujii and H. Ohno, Chem.
Eur. J., 2015, 21, 1463–1467; (b) N. Hamada, Y. Yoshida, S.
Oishi and H. Ohno, Org. Lett., 2017, 19, 3875–3878.
15 For the pioneering work, see: (a) D. J. Gorin, N. R. Davis and
Notes and references
1
2
For reviews, see: (a) A. W. Schmidt, K. R. Reddy and H.‐J.
Knölker, Chem. Rev., 2012, 112, 3193−3328; (b) J.‐P.
Lellouche, R. R. Koner and S. Ghosh, Rev. Chem. Eng., 2013,
29, 413−437; (c) A. Venkateswararao and K. R. J. Thomas,
Solar Cell Nanotechnology, 2014, 41−96.
F. D. Toste, J. Am. Chem. Soc., 2005, 127, 11260–11261; for a
review, see: (b) P. W. Davies and M. Garzón, Asian J. Org.
Chem., 2015, 4, 694–708.
16 (a) A. Wetzel and F. Gagosz Angew. Chem. Int. Ed., 2011, 50
7354–7358; (b) B. Lu, Y. Luo, L. Liu, L. Ye, Y. Wang and L.
Zhang, Angew. Chem. Int. Ed., 2011, 50, 8358–8362.
,
For recent examples, see: (a) C. Jiao, K.‐W. Huang, J. Luo, K.
Zhang, C. Chi and J. Wu, Org. Lett., 2009, 11, 4508–4511; (b)
A. D. Hendsbee, J.‐P. Sun, W. K. Law, H. Yan, I. G. Hill, D. M.
Spasyuk and G. C. Welch, Chem. Mater., 2016, 28, 7098–
7109; (c) S. M. Kim, J. H. Yun, S. H. Han and J. Y. Lee, J. Mater.
17 For related studies based on azide‐derived gold carbenoids,
see: (a) Z.‐Y. Yan, Y. Xiao and L. Zhang, Angew. Chem. Int. Ed.,
2012, 51, 8624–8627; (b) C. Gronnier, G. Boissonnat and F.
Gagosz, Org. Lett., 2013, 15, 4234–4237; (c) N. Li, T. Wang, L.
Gong and L. Zhang, Chem.–Eur. J., 2015, 21, 3585–3588; (d)
C. Shu, Y.‐H. Wang, B. Zhou, X.‐L. Li, Y.‐F. Ping, X. Lu and L.‐W.
Ye, J. Am. Chem. Soc., 2015, 137, 9567–9570; (e) Y. Wu, L.
Chem. C, 2017,
5, 9072–9079.
3
4
For recent reviews, see: (a) N. Yoshikai and Y. Wei, Asian J.
Org. Chem., 2013, 2, 466–478; (b) J. Roy, A. K. Jana and D.
Mal, Tetrahedron, 2012, 68, 6099−6121.
Zhu, Y. Yu, X. Luo and X. Huang, J. Org. Chem., 2015, 80
,
For recent examples of aryl‐annulated [c]carbazole
syntheses, see: (a) M. E. Budén, V. A. Vaillard, S. E. Martin
and R. A. Rossi, J. Org. Chem., 2009, 74, 4490–4498; (b) T.
Chatterjee, G. Roh, M. A. Shoaib, C.‐H. Suhl, J. S. Kim, C.‐G.
Cho and E. J. Cho, Org. Lett., 2017, 19, 1906–1909.
For our recent studies on carbazole synthesis, see: (a) T.
Watanabe, S. Ueda, S. Inuki, S. Oishi, N. Fujii and H. Ohno,
Chem. Commun., 2007, 4516–4518; (b) T. Watanabe, S.
Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2009, 74, 4720–
4726; (c) T. Takeuchi, S. Oishi, T. Watanabe, H. Ohno, J.
Sawada, K. Matsuno, A. Asai, N. Asada, K. Kitaura and N.
Fujii, J. Med. Chem., 2011, 54, 4839–4846.
11407–11416; (f) N. Li, X.‐L. Lian, Y.‐H. Li, T.‐Y. Wang, Z.‐Y.
Han, L. Zhang and L.‐Z. Gong, Org. Lett., 2016, 18, 4178–
4181; (g) C. Shu, Y.‐H. Wang, C.‐H. Shen, P.‐P. Ruan, X. Lu and
L.‐W. Ye, Org. Lett., 2016, 18, 3254–3257; (h) G. H. Lonca, C.
Tejo, H. L. Chan, S. Chiba and F. Gagosz, Chem. Commun.,
2017, 53, 736–739; (i) J. Cai, B. Wu, G. Rong, C. Zhang, L. Qiu
and X. Xu, Org. Lett., 2018, 20, 2733–2736; for oxidative
cyclisation of azido‐diynes for synthesis of fused quinolines
and indoles, see: (j) W.‐B. Shen, Q. Sun, L. Li, X. Liu, B. Zhou,
5
J.‐Z. Yan, X. Lu and L.‐W. Ye, Nat. Commun., 2017, 8, 1748.
18 For pioneering works on gold‐catalysed hydroarylation of
alkynes, see: (a) A. Fürstner and V. Mamane, J. Org. Chem.,
2002, 67, 6264–6267; (b) V. Mamane, P. Hannen and A.
Fürstner, Chem. Eur. J., 2004, 10, 4556–4575; (c) E. Soriano
and J. Marco‐Contelles, Organometallics, 2006, 25, 4542–
4553; for recent theoretical study, see: (d) V. M. Lau, W. C.
Pfalzgraff, T. E. Markland and M. W. Kanan, J. Am. Chem.
Soc., 2017, 139, 4035−4041.
6
7
(a) S. K. Ghosh, B.‐C. Kuo, H.‐Y. Chen, J.‐Y. Li, S.‐D. Liu and H.
M. Lee, Eur. J. Org. Chem., 2015, 4131–4142; (b) X.‐Q. Feng,
F. Zhang, X.‐P. He, G.‐R. Chen, X.‐Y. Wu and F. Sha, RSC Adv.,
2016, 6, 75162–75165; (c) F. Yu, D. Li, Y. Wei, R.‐M. Kang and
Q.‐X. Guo, Tetrahedron, 2018, 74, 1965–1972.
(a) Y. Nagase, H. Shirai, M. Kaneko, E. Shirakawa and T.
Tsuchimoto, Org. Biomol. Chem., 2013, 11, 1456–1459; (b) J.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1‐3 | 9
Please do not adjust margins

Please do not adjust margins
Chemical Science
Page 11 of 10
COMMUNICATION
Journal Name
19 A portion of this study for total synthesis of dictyodendrins
has been already disclosed as a preliminary communication:
J. Matsuoka, Y. Matsuda, Y. Kawada, S. Oishi and H. Ohno,
Angew. Chem. Int. Ed., 2017, 56, 7444–7448.
20 (a) A. Padwa, D. J. Austin, Y. Gareau, J. M. Kassir and S. L. Xu,
J. Am. Chem. Soc., 1993, 115, 2637–2647; for a recent
review, see: (b) K. S. Sindhu, A. P. Thankachan, P. S. Sajitha
and G. Anilkumar, Org. Biomol. Chem., 2015, 13, 6891–6905.
21 The substituent effect at the terminal position is a subject of
future investigation.
(d) J. Steigman and W. Cronkright, J. Am. Chem.VSieowc.A,rt1ic9le7O0n,line
92, 6736–6743.
30 (a) M. Luo, H. Shadnia, G. Qian, X. Du, DDO. YI:u1,0.D10.3M9/aC,8JS.CS0.3525C
Wright and Z. Y. Wang, Chem. Eur. J., 2009, 15, 8902–8908;
(b) Y. Ishigaki, H. Kawai, R. Katoono, K. Fujiwara, H. Higuchi,
H. Kikuchi and T. Suzuki, Can. J. Chem., 2017, 95, 243–252;
(c) M. Walesa‐Chorab and W. G. Skene, ACS Appl. Mater.
Interfaces, 2017, 9, 21524–21531.
22 For a C2‐selective addition of pyrrole in gold‐catalyzed
reaction of alkynes, see: S. Naoe, Y. Suzuki, K. Hirano, Y.
Inaba, S. Oishi, N. Fujii and H. Ohno, J. Org. Chem., 2012, 77
,
4907–4916.
23 In single crystals of 7aF', two crystallographically
independent molecules, both of which were disordered at
the phenyl group.
24 Recrystallisation of 11D‐Me2 from CH2Cl2 gave four
crystallographically independent molecules in the single
crystal lattices, two of which are shown below. As expected,
the indolo[2,3‐c]carbazole core had a planer structure in all
four molecules.
25 (a) S. Pratihar and S. Roy, J. Org. Chem., 2010, 75, 4957–
4963; (b) T. A. Nigst, M. Westermaier, A. R. Ofial and H.
Mayr, Eur. J. Org. Chem., 2008, 2369–2374; for a nucleophilic
reaction of N‐Boc‐pyrrole at the 2‐position, see: (c) J. Tang,
J.‐J. Yue, F.‐F. Tao, G. Grampp, B.‐X. Wang, F. Li, X.‐Z. Liang,
Y.‐M. Shen and J.‐H. Xu, J. Org. Chem., 2014, 79, 7572−7582.
26 D. Pflästerer, S. Schumacher, M. Rudolph and A. S. K.
Hashmi, Chem. Eur. J., 2015, 21, 11585–11589.
27 The C‐H insertion is often observed in gold‐carbenoid
chemistry, see: (a) M. R. Fructos, T. R. Belderrain, P. de
Frémont, N. M. Scott, S. P. Nolan, M. M. Díaz‐Requejo and P.
J. Pérez, Angew. Chem. Int. Ed., 2005, 44, 5284–5288; (b) S.
Bhunia and R.‐S. Liu, J. Am. Chem. Soc., 2008, 130, 16488–
16489; (c) L. Cui, G. Zhang, Y. Peng and L. Zhang, Org. Lett.,
2009, 11, 1225–1228; (d) Y. Horino, T. Yamamoto, K. Ueda, S.
Kuroda and F. D. Toste, J. Am. Chem. Soc., 2009, 131, 2809–
2811; (e) A. S. K. Hashmi, I. Braun, P. Nösel, J. Schädlich, M.
Wieteck, M. Rudolph and F. Rominger, Angew. Chem. Int.
Ed., 2012, 51, 4456–4460; (f) L. Ye, Y. Wang, D. H. Aue and L.
Zhang, J. Am. Chem. Soc., 2012, 134, 31–34; (g) S. Bhunia, S.
Ghorpade, D. B. Huple and R.‐S. Liu, Angew. Chem. Int. Ed.,
2012, 51, 2939–2942; (h) F. Pan, S. Liu, R.‐K. Lin, Y.‐F. Yu, J.‐
M. Zhou and L.‐W. Ye, Chem. Commun., 2014, 50, 10726–
10729; (i) Y. Wang, M. Zarca, L.‐Z. Gong and L. Zhang, J. Am.
Chem. Soc., 2016, 138, 7516–7519; (j) J. E. M. N. Klein, G.
Knizia, L. N. dos Santos Comprido, J. Kästner and A. S. K.
Hashmi, Chem. Eur. J., 2017, 23, 16097–16103.
28 (a) T. Suzuki, T. Tsuji, T. Ohkubo, A. Okada, Y. Obana, T.
Fukushima, T. Miyashi and Y. Yamashita, J. Org. Chem., 2001,
66, 8954–8960; (b) T. Suzuki, Y. Tsubata, Y. Obana, T.
Fukushima, T. Miyashi, H. Kawai, K. Fujiwara and K. Akiyama,
Tetrahedron Lett., 2003, 44, 7881–7884.
29 (a) C. Wurster and R. Sendtner, Ber. Dtsch. Chem. Ges., 1897,
12, 1803; (b) L. Michaelis, M. P. Shubert and S. Granick, J.
Am. Chem. Soc., 1939, 61, 1981–1992; (c) J. R. Bolton, A.
Carringon and J. Santos‐Veiga, Mol. Phys., 1962,
5, 615–619;
10 | J. Name., 2012, 00, 1‐3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins